title: Exploratory analysis of the visceral disease subgroup in a phase III study of abiraterone acetate in metastatic castration-resistant prostate cancer.
abstract: BACKGROUND
  Visceral disease, non-nodal soft-tissue metastases predominantly involving the lung and liver, is a negative prognostic factor in patients with metastatic castration-resistant prostate cancer (mCRPC). An exploratory analysis of COU-AA-301 assessed whether abiraterone acetate (AA) improved overall survival (OS) in mCRPC patients with visceral disease progressing post docetaxel.
  
  
  METHODS
  In COU-AA-301, post-docetaxel mCRPC patients were randomized 2:1 to AA 1000 mg (n=797) or placebo (n=398) once daily, each with prednisone 5 mg b.i.d. The primary end point was OS; secondary end points included radiographic progression-free survival (rPFS), PSA response rate and objective response rate (ORR). Treatment effects in visceral disease (n=352) and non-visceral disease (n=843) subsets were examined using final data (775 OS events).
  
  
  RESULTS
  AA plus prednisone produced similar absolute improvement in median OS in patients with (4.6 months) and without (4.8 months) visceral disease versus prednisone; hazard ratios (HRs) were 0.79 (95% confidence interval (CI): 0.60-1.05; P=0.102) and 0.69 (95% CI: 0.58-0.83; P<0.0001), respectively. Treatment with AA plus prednisone significantly and comparably improved secondary endpoint outcomes versus prednisone in both the subsets: the HRs for rPFS were 0.60 (95% CI: 0.46-0.78; P=0.0002) and 0.68 (95% CI: 0.58-0.80; P<0.0001) in visceral and non-visceral disease subsets, respectively. PSA response rates were 28% versus 7% in the visceral disease subsets and 30% versus 5% in the non-visceral disease subsets (both P<0.0001), and ORRs were 11% versus 0% (P=0.0058) and 19% versus 5% (P=0.0010), respectively. The incidence of grade 3/4 adverse events was similar between the subsets and between the treatment arms in each subset. Adverse events related to CYP17 blockade were increased in the AA arms and were similar in patients with or without visceral disease.
  
  
  CONCLUSIONS
  AA plus prednisone provides significant clinical benefit, including improvements in OS and secondary end points, in post-docetaxel mCRPC patients with or without baseline visceral disease. The presence of visceral disease does not preclude clinical benefit from abiraterone.
authors.affiliation: Department of Medical Oncology, Comprehensive Cancer Centers of Nevada, Las Vegas, NV, USA.
authors.forename: O B
authors.initials: OB
authors.lastname: Goodman
authors.affiliation: University of Colorado Cancer Center, Aurora, CO, USA.
authors.forename: T W
authors.initials: TW
authors.lastname: Flaig
authors.affiliation: Janssen Research & Development, Los Angeles, CA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Molina
authors.affiliation: Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: P F A
authors.initials: PF
authors.lastname: Mulders
authors.affiliation: Institut Gustave Roussy, University of Paris Sud, Villejuif, France.
authors.forename: K
authors.initials: K
authors.lastname: Fizazi
authors.affiliation: Urologikum Hamburg, Hamburg, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Suttmann
authors.affiliation: Janssen Research & Development, Raritan, NJ, USA.
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.affiliation: Janssen Research & Development, Los Angeles, CA, USA.
authors.forename: T
authors.initials: T
authors.lastname: Kheoh
authors.affiliation: The Institute of Cancer Research and The Royal Marsden Hospital, Sutton, UK.
authors.forename: J S
authors.initials: JS
authors.lastname: de Bono
authors.affiliation: Memorial Sloan-Kettering Cancer Center and Weill-Cornell Medical College, New York, NY, USA.
authors.forename: H I
authors.initials: HI
authors.lastname: Scher
mesh_terms: D000069501:Abiraterone Acetate; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000730:Androstadienes / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000077143:Docetaxel; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D011241:Prednisone / Q000008:administration & dosage; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D012307:Risk Factors; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome; D014781:Viscera / Q000473:pathology*
chemical_list: D000730:Androstadienes; D018931:Antineoplastic Agents, Hormonal; D043823:Taxoids; D000077143:Docetaxel; D000069501:Abiraterone Acetate; D011241:Prednisone